Cromarty Ross, Archary Derseree
Centre for the AIDS Programme of Research in South Africa (CAPRISA), Nelson Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Department of Medical Microbiology, University of KwaZulu-Natal, Durban, South Africa.
AIDS Res Treat. 2020 Oct 27;2020:8672850. doi: 10.1155/2020/8672850. eCollection 2020.
The relationship between inflammation and HIV has been a focus of research over the last decade. In HIV-infected individuals, increased HIV-associated immune activation significantly correlated to disease progression. While genital inflammation (GI) has been shown to significantly increase the risk of HIV acquisition and transmission, immune correlates for reduced risk remain limited. In certain HIV-exposed seronegative individuals, an immune quiescent phenotype characterized reduced risk. Immune quiescence is defined by specific, targeted, highly regulated immune responses that hinder overt inflammation or immune activation. Targeted management of inflammation, therefore, is a plausible strategy to mitigate HIV risk and slow disease progression. Nonsteroidal anti-inflammatory drugs (NSAIDs) such as hydroxychloroquine and aspirin have shown encouraging preliminary results in low-risk women by reducing systemic and genital immune activation. A topical NSAID, containing ibuprofen, is effective in treating vulvovaginal inflammation. Additionally, the glucocorticoids (GCs), prednisolone, and dexamethasone are used to treat HIV-associated immune activation. Collectively, these data inform on immune-modulating drugs to reduce HIV risk. However, the prolonged use of these pharmaceutical drugs is associated with adverse effects, both systemically and to a lesser extent topically. Natural products with their reduced side effects coupled with anti-inflammatory properties render them viable options. Lactic acid (LA) has immunomodulatory properties. LA regulates the genital microbiome by facilitating the growth of species, while simultaneously limiting bacterial species that cause microbial dysbiosis and GI. Glycerol monolaurate, besides being anti-inflammatory, also inhibited SIV infections in rhesus macaques. The proposed pharmaceutical and natural products could be used in combination with either antiretrovirals for treatment or preexposure prophylaxis for HIV prevention. This review provides a summary on the associations between inflammation, HIV risk, and disease progression. Furthermore, we use the knowledge from immune quiescence to exploit the use of pharmaceutical and natural products as strategic interventions to manage inflammation, toward mitigating HIV infections.
在过去十年中，炎症与艾滋病病毒（HIV）之间的关系一直是研究的重点。在HIV感染者中，与HIV相关的免疫激活增加与疾病进展显著相关。虽然生殖器炎症（GI）已被证明会显著增加HIV感染和传播的风险，但降低风险的免疫相关因素仍然有限。在某些HIV暴露血清阴性个体中，一种免疫静止表型的特征是风险降低。免疫静止由特定的、有针对性的、高度调节的免疫反应所定义，这些反应会阻碍明显的炎症或免疫激活。因此，针对性地管理炎症是降低HIV风险和减缓疾病进展的一种可行策略。非甾体抗炎药（NSAIDs），如羟氯喹和阿司匹林，通过减少全身和生殖器免疫激活，在低风险女性中显示出令人鼓舞的初步结果。一种含有布洛芬的外用NSAID对治疗外阴阴道炎症有效。此外，糖皮质激素（GCs）、泼尼松龙和地塞米松被用于治疗与HIV相关的免疫激活。总体而言，这些数据为降低HIV风险的免疫调节药物提供了信息。然而，长期使用这些药物会带来全身和较小程度的局部不良反应。具有抗炎特性且副作用较小的天然产物使其成为可行的选择。乳酸（LA）具有免疫调节特性。LA通过促进某些物种的生长来调节生殖器微生物群，同时限制导致微生物失调和GI的细菌物种。单月桂酸甘油酯除了具有抗炎作用外，还能抑制恒河猴的猴免疫缺陷病毒（SIV）感染。所提出的药物和天然产物可与抗逆转录病毒药物联合用于治疗或用于HIV预防的暴露前预防。本综述总结了炎症、HIV风险和疾病进展之间的关联。此外，我们利用免疫静止的知识，开发药物和天然产物作为管理炎症的战略干预措施，以减轻HIV感染。
